Fig. 8
FFA-DHA but not TG-DHA rescues hematopoiesis in apoc2 and lpl mutants. a, b In situ hybridization with runx1/cmyb and β-globin probes in WT, apoc2 and lpl mutants injected with FFA-DHA (a) or TG-DHA (b) at 2 dpf; embryos were fixed at 80 hpf for in situ hybridization. Scale bars, 200 μm. c Schematic representation of the working hypothesis. VLDL delivers both the TG substrate and Apoc2, an obligatory activator of Lpl to the hematopoietic niche. Lpl, expressed on stromal and/or endothelial cells, catalyzes hydrolysis of TG to produce FFAs. Among FFAs released by the Apoc2/Lpl catalysis, the essential fatty acid DHA supports normal hematopoiesis. apoc2 and lpl mutant zebrafish in which TG hydrolysis is blocked, have a defect in HSPC maintenance and differentiation. Administration of DHA as a free fatty acid, but not DHA esterified into a TG, rescues the hematopoiesis defect in apoc2 and lpl mutant zebrafish